Project summary/abstract Traumatic brain injury (TBI) results from a blow to the head and can range in severity from mild (e.g., brief change in mental status or consciousness) to severe (e.g., extended unconsciousness, prolonged amnesia, altered cognitive function). Trauma to the brain is the most likely type of injury to cause death or permanent disability. The costs of TBI to our society are enormous when measured by any criterion. In the general population, the risk of TBI is fairly constant throughout the lifespan, but military personnel are at much higher risk. In fact, TBI has been coined the signature injury suffered by soldiers and marines serving in Afghanistan and Iraq and accounts for about 30% of all combat casualties. It has been estimated that 10-20% of veterans of the current conflicts (150,000-300,000) have TBI of some kind. TBI is most accurately classified as a polytrauma in light of the fact that multiple organ systems can be altered. What is more, the effects of even mild TBI are cumulative and can increase the risk of co-morbid illnesses involving the central nervous system such as PTSD and Parkinson's disease. Substance abuse and alcohol abuse in particular, is a major complicating factor in TBI and should also be considered as a co-occurring condition in its own right. Alcohol abuse is steadily increasing among active military personnel and has long been a serious affliction among veterans. Like TBI, alcohol abuse can cause damage to the CNS but very little is known about how alcohol influences the severity and outcome of TBI. Recognizing that alcohol abuse and TBI are bi-directionally related for risk and consequences, the goal of research in this application is to achieve a better understanding of how these two conditions interact to determine long-term outcomes. To achieve this goal, Specific Aim 1 will analyze how binge alcohol intake prior to TBI alters the major signs and symptoms of brain injury to include edema, hypoperfusion, increased inflammation, neuronal damage, and diminished cognitive ability. Specific Aim 2 will evaluate these same outcome measures when binge alcohol treatment follows TBI. Specific Aim 3 will determine if TBI subsequently increases voluntary intake of alcohol. We will use validated mouse models of closed head injury and binge alcohol intoxication to pursue the goals of this application.